OBJECTIVE: To determine whether essential hypertensive patients with high Na+,K+,Cl- cotransport (COT) display alterations of some indices of kidney tubular reabsorption similar to those observed in Milan hypertensive (MHS) rats, which have high COT in both erythrocytes and kidney tubular cells, and hypertension caused by a primary increase of tubular reabsorption. DESIGN: Two sets of experiments were performed. First, renal function in two subgroups of hypertensive patients (one with 'high' and one with 'normal' COT was compared with that in normotensive controls. Secondly, the natriuretic and diuretic effects of a single oral dose of frusemide (25 mg) were analysed in six high- and in six normal- COT hypertensive patients. RESULTS: Compared with normotensives and with normal-COT hypertensives, high-COT hypertensives had lower fractional uric acid excretion and plasma renin activity with similar glomerular filtration rate and urinary sodium and potassium excretion. COT was negatively correlated with fractional uric acid excretion in the essential hypertensive patients but not in the normotensives. The diuretic natriuretic response to frusemide was much higher in high- than in normal-COT hypertensives. CONCLUSION: These results are consistent with the hypothesis that patients with high COT have abnormal renal handling of sodium similar to that observed in MHS rats.